Prostate cancer is a leading cause of morbidity and mortality among men. Risk factors for prostate cancer have remained elusive and aside from age, having a family history of the disease or African ancestry, until recently, no genetic or non-genetic (i.e. lifestyle) risk factors have been consistently demonstrated to contribute to variation in disease risk in the population. Over the past year, we contributed to the first reproducible genetic risk factor for prostate cancer at 8q24. Through fine-mapping of 8q24 in five racial/ethnic populations in the Multiethnic Cohort Study (MEC), we identified three regions that contain 7 independent risk variants for prostate cancer. Only some of these variants were found in studies conducted in European Whites, thus, emphasizing the power of genetic studies in multiple racial/ethnic populations to reveal a more complete spectrum of variants associated with disease risk. In this application, we propose to work with the GEI-GWA Steering Committee to identify genetic factors that contribute to prostate cancer by performing a well-powered genome-wide association study among African American, Japanese American, Native Hawaiian, Latino and European American men in the MEC. More specifically, we propose the genotyping of approximately 1,000,000 single nucleotide polymorphisms (SNPs) and >940,000 probes to detect copy number variation in 3,750 prostate cancer cases and 3,750 controls, to identify pan-ethnic genetic variants that affect risk in all five racial/ethnic populations, as well as important ethnic-specific variation. In this multi-ethnic dataset, we will also examine interaction between associated variants, environmental factors (thereby better defining the role of these factors) and disease severity, as well as explore the causes of heterogeneity of genetic effects across populations. We have also established collaborations with other prostate cancer researches to replicate the ethnic-specific associations observed in this GWA study in minority populations. We expect this work to significantly advance knowledge of the etiology of prostate cancer across these racial/ethnic populations, guiding the development of future preventive, early detection, prognostic and even therapeutic measures.